Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak)

NCT ID: NCT00632827

Last Updated: 2020-04-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-01
• Study Completion Date: 2016-06-23

Brief Summary

This study examines the use of denileukin diftitox (Ontak) for patients with peripheral T-cell lymphoma who are candidates for autologous stem cell transplants.

Detailed Description

This protocol proposes first to increase the proportion of patients who achieve adequate initial disease control and are able to proceed to autologous stem cell transplant (ASCT) in first complete or partial remission. It administers intensive and novel induction therapy.

Two cycles of gemcitabine, vinorelbine, Doxil (GND) will be used followed by two cycles of augmented dose Cyclophosphamide (CHOP) plus high-dose methotrexate (MTX). Patients will be restaged after two cycles of GND to assess response to GND alone and again after the second cycle of augmented CHOP/high-dose MTX.

Those achieving a remission status will receive intensive consolidation with HiDAC/etoposide followed by stem cell mobilization. A five-day course of denileukin diftitox (Ontak) will be administered at and will serve as an in vivo purge. This will be followed by autologous stem cell transplant.

Those not achieving partial remission or better following the four induction courses will receive 2 cycles of denileukin diftitox(Ontak) for 5 days. Those achieving partial remission or better to this regimen will go on to consolidation/mobilization and autologous stem cell transplant.

Post-transplant, denileukin diftitox will also be used as an additional module of therapy.

Conditions

Peripheral T-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Plan

(1) Induction Chemo A; Two 21-day cycles of Gemcitabine 1000 mg/m2 days (D) 1, 8, Navelbine 20 mg/m2 D1, D8; Doxil 15 mg/m2 Days 1 and 8, G-CSF Days 4-6 and 10-15 (2) Induction Chemo B: Two 21-day cycles of Cyclophosphamide 2000 mg/m2 day 1; Doxorubicin 50 mg/m2 day 1; Vincristine 1.4 mg/m2 day 1; Prednisone 100 mg/m2 days 1-5; Methotrexate 3000 mg/m2 IV over 4h day 15; Leucovorin rescue (3) Disease Evaluation (4) High-dose Consolidation Chemo, high dose Ara-C, Denileukin diftitox (Ontak) and Stem Cell Collection (5) Consolidation Cytarabine 2000 mg/m2 IV over 2 h q 12h days 1-4, Etoposide 40 mg/m2 continuous intravenous infusion (CIVI), days 1-4, Denileukin Diftitox (Ontak) 9 mcg/kg/day days 6-10, G-CSF 10 mcg/kg/day day 14+, Stem cell collection day 22 (6) Autologous Stem Cell Transplant Carmustine 550 mg/m2 day -6, Etoposide 60 mg/kg IV over 4h day -4, Cyclophosphamide 100 mg/kg day -2, Stem cell infusion D0 (7) Post-transplant: Denileukin Diftitox (Ontak) 18 mcg/kg/day days 1- 5

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Chemotherapy medication used to treat a number of types of cancer

Navelbine

Intervention Type: DRUG

Navelbine is an chemotherapy medication used to treat a number of types of cancer

Doxorubicin Hydrochloride Liposome Injection

Intervention Type: DRUG

Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug

Granulocyte-colony stimulating factor (G-CSF)

Intervention Type: DRUG

G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

Pegfilgrastim

Intervention Type: DRUG

Colony-stimulating factor 3 (CSF 3) and, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. May be used instead of G-CSF

Cyclophosphamide

Intervention Type: DRUG

Cancer medication that interferes with the growth and spread of cancer cells in the body

Vincristine

Intervention Type: DRUG

Vincristine is a chemotherapy medication used to treat cancer. Vincristine works by stopping the cancer cells from separating into 2 new cells to stops the growth of the cancer

Leucovorin

Intervention Type: DRUG

Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.

Methotrexate

Intervention Type: DRUG

Methotrexate is a chemotherapy medication used to treat cancer

Doxorubicin Hydrochloride

Intervention Type: DRUG

Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer

Cytarabine

Intervention Type: DRUG

Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma

Etoposide

Intervention Type: DRUG

Etoposide is a is a chemotherapy medication used to treat cancer

Carmustine

Intervention Type: DRUG

Carmustine is a chemotherapy medication used to treat cancer

Denileukin diftitox

Intervention Type: DRUG

Denileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. Denileukin diftitox could bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells

Interventions

Gemcitabine

Chemotherapy medication used to treat a number of types of cancer

Intervention Type: DRUG

Navelbine

Navelbine is an chemotherapy medication used to treat a number of types of cancer

Intervention Type: DRUG

Doxorubicin Hydrochloride Liposome Injection

Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug

Intervention Type: DRUG

Granulocyte-colony stimulating factor (G-CSF)

G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

Intervention Type: DRUG

Pegfilgrastim

Colony-stimulating factor 3 (CSF 3) and, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. May be used instead of G-CSF

Intervention Type: DRUG

Cyclophosphamide

Cancer medication that interferes with the growth and spread of cancer cells in the body

Intervention Type: DRUG

Vincristine

Vincristine is a chemotherapy medication used to treat cancer. Vincristine works by stopping the cancer cells from separating into 2 new cells to stops the growth of the cancer

Intervention Type: DRUG

Leucovorin

Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.

Intervention Type: DRUG

Methotrexate

Methotrexate is a chemotherapy medication used to treat cancer

Intervention Type: DRUG

Doxorubicin Hydrochloride

Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer

Intervention Type: DRUG

Cytarabine

Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma

Intervention Type: DRUG

Etoposide

Etoposide is a is a chemotherapy medication used to treat cancer

Intervention Type: DRUG

Carmustine

Carmustine is a chemotherapy medication used to treat cancer

Intervention Type: DRUG

Denileukin diftitox

Denileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. Denileukin diftitox could bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells

Intervention Type: DRUG

Other Intervention Names

Gemzar; Vinorelbine; Doxil; G-CSF; Neulasta; Cyclophosphamide 2000 MG; Cytoxan; Vincrex; Vincasar PFS; Oncovin; Wellcovorin; Rheumatrex; Trexall; Adriamycin; Ara-C; HiDAC; Etopophos; BCNU; Ontak

Eligibility Criteria

Inclusion Criteria

• Histologic diagnosis of any of the following:

• Peripheral T-cell lymphoma not otherwise specified (PTCL-U),(IPI >2)
• Angioimmunoblastic T-cell lymphoma (AILT) (IPI >2)
• Non-primary cutaneous Alk-1-negative anaplastic large cell lymphoma
• Extranodal natural killer (NK)/T lymphoma (Excluding stage I/II nasal disease)
• Blastic NK cell lymphoma
• Enteropathy type T-cell lymphoma
• Cutaneous panniculitis-like T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Measurable or assessable disease is not required.
• Age ≥ 18 and ≤ 70 years
• Previously untreated or 1 prior cycle of chemotherapy
• Creatinine < 2.0 mg/dL
• Total bilirubin < 2.0 mg/dL, aspartate aminotransferase (AST) < 3x upper limit of normal
• Patients who test positive for Hepatitis B surface Ag (HepBSAg) or Hepatitis C antibody (HepCAb) are eligible provided all of the following criteria are met:

• bilirubin ≤ 2 x upper limit of normal;
• aspartate aminotransferase (AST) ≤ 3 x upper limit of normal;
• liver biopsy demonstrates ≤ grade 2 fibrosis and no cirrhosis.

Hepatitis B surface Ag(+) patients will be treated with lamivudine (3TC) or investigator's preferred antiviral regimen throughout protocol therapy and for 6-12 months thereafter.

• Neutrophils ≥ 1000/microlitre (uL) platelets > 100,000/uL
• HIV-negative
• Left ventricular ejection fraction (LVEF) of ≥ 45%
• No known hypersensitivity to denileukin diftitox or any of its components: diptheria toxin, interleukin-2, or excipients
• Non-pregnant, non-nursing: Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
• Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible. (This includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases inImmunoglobulin M (IgM) following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis). Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.

Exclusion Criteria

• PTCL-U / AILT with IPI 0 or 1 Extranodal NK/T nasal stage I/II T-lymphoblastic lymphoma Adult T-cell leukemia/lymphoma
• Adult T-cell leukemia/lymphoma

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence Kaplan, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Washington University

St Louis, Missouri, United States

Countries

United States

Other Identifiers

NCI-2011-01285

Identifier Type: REGISTRY

Identifier Source: secondary_id

072518

Identifier Type: -

Identifier Source: org_study_id